Process for the Production of Cyclic Diketones

ABSTRACT

The present invention relates to a process for the preparation of compounds of formula (I), wherein the substituents are as defined in claim  1,  by reacting a compound of formula (II), either with a chlorination or bromination agent or with a compound of formula (III) CI-SO 2 R 9 , R 9  being C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, phenyl or C 1 -C 4 alkyl-substituted phenyl, to form the compound of formula (IV), reacting the compound of formula (IV) with a compound of formula (V) M + —O − —C(O)—Y wherein Y is as defined above and M +  is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, to form the compound of formula (VI) and treating that compound with a cyanide source in the presence of a base.

The present invention relates to a process for the preparation of cyclic 1,3-diketone derivatives carbonylated in the 2-position.

Processes for the preparation of cyclic 1,3-diketones substituted in the 2-position by an arylcarbonyl group are described, for example, in WO/0015615, WO 00/37437, WO 01/66522 and WO 01/94339. The compounds disclosed therein have herbicidal action.

According to WO 01/94339, such cyclic 1,3-diketones can be prepared by

a) reacting a compound of formula A

wherein Y₁ is a leaving group such as, for example, halogen or cyano and R is an organic substituent, in an inert, organic solvent, in the presence of a base, with a cyclohexanedione of formula B

wherein R is an organic substituent, to form compounds of formula C

and then isomerising those compounds, for example in the presence of a base and a catalytic amount of dimethylaminopyridine or a cyanide source.

However, such processes have the disadvantage that, in order to prepare the starting compounds of formula A from the acid on which they are based, an additional activation step is required for introduction of the leaving group. A further problem in the preparation of the compound of formula A is the instability of the starting compounds and the instability of the compound of formula A itself, which frequently makes the reaction procedure difficult. This is a serious disadvantage especially for large-scale production.

The problem of the present invention is accordingly to make available a novel general process for the preparation of monocyclic and bicyclic 1,3-diketones which makes it possible to prepare such compounds in high yields and good quality with a simple reaction procedure and little outlay without the above-mentioned disadvantages of the known processes.

The present invention accordingly relates to a process for the preparation of compounds of formula I

wherein Y is an organic substituent which is so selected that the compound of formula I has a pK value of from 1 to 5;

A₁ is CR₁R₂;

A₂ is oxygen, C(O), SO₂ or (CR₃R₄)_(n);

n is 1 or 2;

A₃ is CR₅R₆;

R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others C₁-C₄alkyl which may be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, phenyl or by heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others hydrogen, C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, phenyl or heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or

R₁ and R₂ together form a 3- to 5-membered carbocyclic ring which may be substituted by C₁-C₄alkyl and/or interrupted by oxygen, sulfur, S(O), SO₂, OC(O), NR₇ or by C(O); and/or

R₂ and R₄ together or R₂ and R₅ together form a C₁-C₃alkylene chain which may be interrupted by oxygen, sulfur, SO, SO₂, OC(O), NR₈ or by C(O); it being possible for that C₁-C₃alkylene chain in turn to be substituted by C₁-C₄alkyl; and

R₇ and R₈ are each independently of the other C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl or C₁-C₄alkoxycarbonyl; in which process

a) a compound of formula II

wherein A₁, A₂ and A₃ are as defined for formula I, is reacted, in the presence of a water-immiscible solvent, in the presence of a base or a catalytic amount of a tertiary amide, either with a chlorination or bromination agent or with a compound of formula III Cl—SO₂R₉   (III ), wherein R₉ is C₁-C₄alkyl, C₁-C₄haloalkyl, phenyl or C₁-C₄alkyl-substituted phenyl, to form the compound of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z₁ is chlorine, bromine or OSO₂R₉, R₉ being as defined hereinbefore;

b) the compound of formula IV is converted, using a compound of formula V M⁺—O⁻—C(O)—Y   (V), wherein Y is as defined hereinbefore and M⁺ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, preferably hydrogen, the sodium ion or ammonium ion, into the compound of formula VI

and

c) then the compound of formula VI is treated with a cyanide source in the presence of a base.

The organic substituent Y may be a substituent of any desired structure provided that it remains substantially inert under the reaction conditions of the process according to the invention.

Y is preferably a mono-, di- or tri-substituted phenyl, pyridyl or heteroaryl group, especially a di- or tri-substituted phenyl group or a di-substituted 2-pyridyl or 3-pyridyl group, the substitution pattern of those groups being freely selectable provided that the groups remain substantially inert under the reaction conditions of the process according to the invention. Preference is given to phenyl, 3-pyridyl and heteroaryl groups which carry at least one substituent located, very especially, in the ortho position.

Especially advantageously, it is possible, using the process according to the invention, to prepare compounds of formula I wherein

Y is

wherein

A₄ is CRa₁ or ═N—(O)_(p);

p is 0 or 1;

Ra₁ is hydrogen, C₁-C₆alkyl, hydroxy, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylsulfonyloxy, phenylsulfonyloxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆alkylamino, di(C₁-C₆alkyl)amino, C₁-C₃alkoxy-C₁-C₃alkylamino, C₁-C₃alkoxy-C₁-C₃alkyl-N(C₁-C₃alkyl)-, C₁-C₄alkoxycarbonyl, C₁-C₆haloalkyl, formyl, cyano, halogen, phenyl or phenoxy, it being possible for the phenyl-containing groups in turn to be substituted by C₁-C₃alkyl, C₁-C3haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro;

or Ra₁ is a three- to ten-membered monocyclic or together with Ra₂ or Ra₅ annellated bicyclic ring system which may be interrupted once or up to three times by heterocyclic substituents selected from oxygen, sulfur, S(O), SO₂, N(Ra₆), carbonyl and C(═NORa₇), the ring system, unless it is annellated, being bonded to the carbon atom of the substituent A₄ either directly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene or C₂-C₄alkynylene bridge which may be interrupted by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl or by sulfonyl, and the ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system may in turn be mono-, di- or tri-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₃-C₆alkenylthio, C₃-C₆haloalkenylthio, C₃-C₆alkynylthio, C₁-C₄alkoxy-C₁-C₂alkylthio, C₁-C₄alkylcarbonyl-C₁-C₂alkylthio, C₁-C₄alkoxycarbonyl-C₁-C₂alkylthio, cyano-C₁-C₄alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, di(C₁-C₄alkyl)amino, halogen, cyano, nitro, phenyl, benzyloxy and/or by benzylthio, and it being possible for the phenyl-containing groups in turn to be substituted on the phenyl ring by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro, and substituents on the nitrogen in the heterocyclic ring are other than halogen;

or Ra₁ is the group -X₅-X₇ or the group -X₆-X₅-X₇; wherein

X₅ is oxygen, —O(CO)—, —(CO)O—, —O(CO)O—, —N(C₁-C₄alkyl)—O—, —O—N(C₁-C₄alkyl)-, sulfur, sulfinyl, sulfonyl, —SO₂N(C₁-C₄alkyl)-, —N(C₁-C₄alkyl)SO₂—, —N(C₁-C₂alkoxy-C₁-C₂alkyl)SO₂— or

—N(C₁-C₄alkyl)-;

X₆ is a C₁-C₆alkylene, C₃-C₆alkenylene or C₃-C₆alkynylene chain which may be mono- or poly-substituted by halogen or by X₈, the unsaturated bonds of the chain not being bonded directly to the substituent X₅;

Ra₆ is hydrogen, C₁-C₄alkyl, C₁-C₄alkylthio-C₁-C₄alkylcarbonyl, C₁-C₄alkylsulfinyl-C₁-C₄alkylcarbonyl, C₁-C₄alkylsulfonyl-C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylcarbonyl, phenylcarbonyl or phenyl, it being possible for the phenyl groups in turn to be substituted by C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C₄haloalkoxy, C₁-C₄alkylcarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkyl- SO₂, C₁-C₄alkyl-S(O)₂O, C₁-C₄haloalkylthio, C₁-C₄haloalkylsulfinyl, C₁-C₄haloalkyl-SO₂, C₁-C₄haloalkyl-S(O)₂O, C₁-C₄alkyl-S(O)₂NH, C₁-C₄alkyl-S(O)₂N(C₁-C₄alkyl)-, halogen, nitro or by cyano;

Ra₇ is hydrogen, C₁-C₄alkyl, C₃-C₄alkenyl, C₃-C₄alkynyl or benzyl;

Ra₂ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl; vinyl substituted by C₁-C₂alkoxycarbonyl or by phenyl; or C₂-C₆alkynyl, C₂-C₆haloalkynyl; or ethynyl substituted by trimethylsilyl, hydroxy, C₁-C₆alkoxy, C₁-C₄alkoxycarbonyl or by phenyl;

C₃-C₆allenyl, C₃-C₆cycloalkyl or halo- or C₁-C₃alkoxymethyl-substituted C₃-C₆cycloalkyl; or

C₁-C₆alkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆haloalkenyloxy, cyano-C₁-C₄alkoxy, C₁-C₄alkoxy-C₁-C₄alkoxy, C₁-C₄alkylthio-C₁-C₄alkoxy, C₁-C₄alkylsulfinyl-C₁-C₄alkoxy, C₁-C₄alkylsulfonyl-C₁-C₄alkoxy, C₁-C₄alkoxycarbonyl-C₁-C₄alkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl, C₁-C₄alkoxycarbonyl-C₁-C₄alkylthio, C₁-C₄alkoxycarbonyl-C₁-C₄alkylsulfinyl, C₁-C₄alkoxycarbonyl-C₁-C₄alkylsulfonyl, C₁-C₆alkylamino, di(C₁-C₆-alkyl)amino, C₁-C₃alkoxy-C₁-C₃alkylamino, C₁-C₃alkoxy-C₁-C₃alkyl-N(C₁-C₃alkyl), C₁-C₆-alkylaminosulfonyl, di(C₁-C₆alkyl)aminosulfonyl, C₁-C₄alkylsulfonyloxy, C₁-C₄haloalkylsulfonyloxy, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl), cyano, carbamoyl, C₁-C₄alkoxycarbonyl, formyl, halogen, rhodano, amino, hydroxy-C₁-C₄alkyl, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl, C₁-C₄alkylsulfonyl-C₁-C₄alkyl, cyano-C₁-C₄alkyl, C₁-C₆alkylcarbonyloxy-C₁-C₄alkyl, C₁-C₄alkoxycarbonyl-C₁-C₄-alkyl, C₁-C₄alkoxycarbonyloxy-C₁-C₄alkyl, rhodano-C₁-C₄alkyl, phenyl-C₁-C₄alkyl, phenoxy-C₁-C₄alkyl, benzyloxy-C₁-C₄alkyl, benzoyloxy-C₁-C₄alkyl, (2-oxiranyl)-C₁-C₄alkyl, C₁-C₄-alkylamino-C₁-C₄alkyl, di(C₁-C₄alkyl)amino-C₁-C₄alkyl, C₁-C₁₂alkylthiocarbonyl-C₁-C₄alkyl or formyl-C₁-C₄alkyl, benzylthio, benzylsulfinyl, benzylsulfonyl, benzyloxy, benzyl, phenyl, phenoxy, phenylthio, phenylsulfinyl or phenylsulfonyl; it being possible for the phenyl-containing groups in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro; or

Ra₂ is a three- to ten-membered monocyclic or annellated bicyclic ring system which may be aromatic, saturated or partially saturated and may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, the ring system being bonded to the group Q₁ or Q₂ directly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene or C₂-C₄alkynylene bridge which may be interrupted by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl, sulfonyl or by carbonyl; and each ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system may in turn be mono-, di- or tri-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, hydroxy, mercapto, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₃-C₆alkenylthio, C₃-C₆haloalkenylthio, C₃-C₆alkynylthio, C₁-C₄alkoxy-C₁-C₃alkylthio, C₁-C₄alkylcarbonyl-C₁-C₃alkylthio, C₁-C₄alkoxycarbonyl-C₁-C₃alkylthio, cyano-C₁-C₃alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, di(C₁-C₄alkyl)amino, halogen, cyano, nitro, phenyl and/or by benzylthio; it being possible for phenyl and benzylthio in turn to be substituted on the phenyl ring by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro, and substituents on the nitrogen in the heterocyclic ring are other than halogen; or

Ra₂ is the group -X₁-X₃ or the group -X₂-X₁-X₃; wherein

X, is oxygen, —O(CO)—, —(CO)O—, —O(CO)O—, —N(C₁-C₄alkyl)—O—, —O—N(C₁-C₄alkyl)-, thio, sulfinyl, sulfonyl, —SO₂N(C₁-C₄alkyl)-, —N(C₁-C₄alkyl)SO₂—, —N(C₁-C₂alkoxy-C₁-C₂alkyl)SO₂— or —N(C₁-C₄alkyl)-;

X₂ is a C₁-C₆alkylene, C₃-C₆alkenylene or C₃-C₆alkynylene chain which may be mono- or poly-substituted by halogen or by X₄, the unsaturated bonds of the chain not being bonded directly to the substituent X₁;

X₃ and X₇ are each independently of the other a C₁-C₈alkyl, C₃-C₆alkenyl or C₃-C₆alkynyl group which may be mono-, di- or tri-substituted by halogen, hydroxy, amino, formyl, nitro, cyano, mercapto, carbamoyl, C₁-C₆alkoxy, C₁-C₆alkoxycarbonyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆cycloalkyl or halo-substituted C₃-C₆cycloalkyl; or by C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆haloalkenyloxy, cyano-C₁-C6-alkoxy, C₁-C₆alkoxy-C₁-C₆alkoxy, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkoxy, C₁-C₆alkylthio-C₁-C₆alkoxy, C₁-C₆alkylsulfinyl-C₁-C₆alkoxy, C₁-C₆alkylsulfonyl-C₁-C₆alkoxy, C₁-C₆alkoxycarbonyl-C₁-C₆alkoxy, C₁-C₆alkoxycarbonyl, C₁-C₆alkylcarbonyl, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl; oxiranyl which may in turn be substituted by C₁-C₆alkyl; (3-oxetanyl)-oxy which may in turn be substituted by C₁-C₆alkyl; benzyloxy, benzylthio, benzylsulfinyl, benzylsulfonyl, C₁-C₆alkylamino, di(C₁-C₆alkyl)amino, C₁-C₄alkyl-S(O)₂O—, di(C₁-C₄alkyl)aminosulfonyl, rhodano, phenyl, phenoxy, phenylthio, phenylsulfinyl or by phenylsulfonyl; and it being possible for the phenyl- or benzyl-containing groups in turn to be substituted by one or more C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, halogen, cyano, hydroxy or nitro groups; or

X₃ and X₇ are phenyl which may be mono- or poly-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, halogen, cyano, hydroxy or by nitro; or

X₃ and X₇ are each independently of the other C₃-C₆cycloalkyl, C₁-C₆alkoxy- or C₁-C₆alkyl-substituted C₃-C₆cycloalkyl, 3-oxetanyl or C₁-C₆alkyl-substituted 3-oxetanyl; or

X₃ and X₇ are each independently of the other a three- to ten-membered monocyclic or annellated bicyclic ring system which may be aromatic, saturated or partially saturated and may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, the ring system being bonded to the substituent X₁ or X₅ directly or by way of a C₁-C₄alkylene, C₂-C₄alkenylene, C₂-C₄alkynylene, —N(C₁-C₄alkyl)-C₁-C₄alkylene, —S(O)-C₁-C₄alkylene or —SO₂-C₁-C₄alkylene group, and each ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system may in turn be mono-, di- or tri-substituted by C₁-C₆alkyl, C₁-C6haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy, hydroxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, mercapto, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₃-C₆alkenylthio, C₃-C₆haloalkenylthio, C₃-C6-alkynylthio, C₁-C₃alkoxy-C₁-C₃alkylthio, C₁-C₄alkylcarbonyl-C₁-C₂alkylthio, C₁-C₄alkoxycarbonyl-C₁-C₂alkylthio, cyano-C₁-C₃alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₂alkylaminosulfonyl, di(C₁-C₂alkyl)aminosulfonyl, di(C₁-C₄alkyl)amino, C₁-C₆carbonylamino, halogen, cyano, nitro, phenyl, benzyloxy and/or by benzylthio, it being possible for the phenyl groups in turn to be substituted on the phenyl ring by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro, and the substituents on the nitrogen in the heterocyclic ring are other than halogen; and

X₄ and X₈ are each independently of the other hydroxy, C₁-C₆alkoxy, (C₃-C₆cycloalkyl)oxy, C₁-C₆alkoxy-C₁-C₆alkoxy, C₁-C₆alkoxy-C₁-C₆alkoxy-C₁-C₆alkoxy or C₁-C₆alkylsulfonyloxy;

Ra₃ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl, amino, C₁-C₆alkylamino, di(C₁-C₆alkyl)amino, C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl)-, C₁-C₆alkylaminosulfonyl, di(C₁-C₆alkyl)aminosulfonyl, cyano, halogen, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl, C₁-C₄alkylsulfonyl-C₁-C₄alkyl, phenyl, phenylthio, phenylsulfinyl, phenylsulfonyl or phenoxy, it being possible for the phenyl groups in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro;

Ra₄ is hydrogen, C₁-C₆alkyl, hydroxy, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy, C₁-C₄alkylcarbonyloxy, C₁-C₄alkylsulfonyloxy, phenylsulfonyloxy, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₄alkoxycarbonyl, C₁-C₄haloalkyl, formyl, cyano, halogen, phenyl or phenoxy; it being possible for the phenyl-containing groups in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro; or Ra₄ is a three- to ten-membered monocyclic or with Ra₃ or Ra₅ annellated bicyclic ring system which may contain from 1 to 4 hetero atoms selected from nitrogen, oxygen and sulfur, the ring system, unless it is annellated, being bonded to the group Q₁ or Q₂ either directly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene or C₂-C₄alkynylene bridge which may be interrupted by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl, sulfonyl or by carbonyl; and the ring system may contain not more than 2 oxygen atoms and not more than two sulfur atoms, and the ring system may in turn may be mono-, di- or tri-substituted by C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₃-C₆alkenylthio, C₃-C₆haloalkenylthio, C₃-C₆alkynylthio, C₁-C₄alkoxy-C₁-C₂alkylthio, C₁-C₄alkylcarbonyl-C₁-C₂alkylthio, C₁-C₄alkoxycarbonyl-C₁-C₂alkylthio, cyano-C₁-C₄alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, aminosulfonyl, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, amino, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, halogen, cyano, nitro, phenyl and/or by benzylthio; it being possible for phenyl and benzylthio in turn to be substituted on the phenyl ring by C₁-C₃alkyl, C₁-C3haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro, and substituents on the nitrogen in the heterocyclic ring are other than halogen;

Ra₅ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₂-C₆haloalkynyl, C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl, C₁-C₆alkylsulfonyloxy, hydroxy, mercapto, amino, C₁-C₆alkylamino, di(C₁-C₆alkyl)amino, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl)-, C₁-C₆alkylaminosulfonyl, di(C₁-C₆alkyl)aminosulfonyl, cyano, halogen, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl, C₁-C₄alkylsulfonyl-C₁-C₄alkyl, triazolyl, phenyl, phenylthio, phenylsulfinyl, phenylsulfonyl or phenoxy; it being possible for the phenyl-containing groups to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro; and agronomically acceptable salts/N-oxides/isomers/enantiomers of those compounds.

The alkyl groups appearing in the above substituent definitions may be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. Alkoxy, alkenyl and alkynyl radicals are derived from the mentioned alkyl radicals. The alkenyl and alkynyl groups may be mono- or poly-unsaturated. Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy. Alkoxycarbonyl is, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl or tert-butoxycarbonyl; preferably methoxycarbonyl or ethoxycarbonyl.

Halogen is generally fluorine, chlorine, bromine or iodine. The same applies also to halogen in conjunction with other meanings, such as haloalkyl or halophenyl. Haloalkyl groups having a chain length of from 1 to 6 carbon atoms are, for example, fluoromethyl, difluoromethyl, chlorodifluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1-fluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-fluoroprop-2-yl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoroethyl and 2,2,2-trichloroethyl, pentafluoroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl.

Alkenyl and alkynyl groups may be mono- or poly-unsaturated, so that alkyl, alkenyl and alkynyl chains having one or more double or triple bonds are also included. Alkenyl is, for example, vinyl, allyl, isobuten-3-yl, CH₂═CH—CH₂—CH═CH—, CH₂═CH—CH₂—CH₂—CH═CH— or CH₃—CH═CH—CH₂—CH═CH—. A preferred alkynyl is, for example, propargyl, and a preferred allenyl is CH₂═C═CH₂—.

An alkylene chain may also be substituted by one or more C₁-C₃alkyl groups, especially by methyl groups. Such alkylene chains and alkylene groups are preferably unsubstituted. The same applies also to all groups containing C₃-C₆cycloalkyl, C₃-C₅oxacycloalkyl, C₃-C₅thiacycloalkyl, C₃-C₄dioxacycloalkyl, C₃-C₄dithiacycloalkyl or C₃-C₄oxathiacycloalkyl, which occur, for example, also as part of oxygen- and sulfur-containing heterocyclic ring systems of the radicals Ra₁ and Ra₂.

A C₁-C₄alkylene, C₁-C₄alkenylene or C₂-C₄alkynylene chain which may be interrupted by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl or by sulfonyl, or in X₂ or X₆ in the meaning of a C₁-C₆alkylene, C₃-C₆alkenylene or C₃-C₆alkynylene chain which may be mono- or poly-substituted by halogen or by X₄ or X₈, and wherein the unsaturated bonds of the chain are not bonded directly to the substituent X₁ or X₅, is to be understood as being, for example —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂—, —CH₂CH₂CH₂CH₂—, —CH(CH₃)—, —CH₂CH(CH₃)—, —CH₂CH(CH₃)CH₂—, —CH₂CH(Cl)CH₂—, —CH₂CH(OCH₃)CH₂—, —CH₂O—, —OCH₂—, —CH₂OCH₂—, —OCH₂CH₂—, —OCH₂CH₂CH₂—, —CH₂OCH₂CH₂—, —CH₂OCH(CH₃)CH₂—, —SCH₂—, —SCH₂CH₂—, —SCH₂CH₂CH₂—, —CH₂S—, —CH₂SCH₂—, —CH₂S(O)CH₂—, —CH₂SO₂CH₂—, —CH₂SCH₂CH₂—, —CH₂S(O)CH₂CH₂—, —CH₂SO₂CH₂CH₂—, —CH₂SO₂NH—, —CH₂N(CH₃)SO₂CH₂CH₂—, —N(SO₂Me)CH₂CH₂—, —CH₂C(O)NH— or —CH₂NHC(O)CH₂—. A C₂-C₄alkenylene chain which may be interrupted by oxygen is accordingly to be understood as being, for example, —CH═CH—CH₂—, —CH═CH—CH₂CH₂— or —CH═CHCH₂OCH₂—, and a C₂-C₄alkynylene chain which may be interrupted by oxygen is to be understood as being, for example, —C≡C—, —C≡CCH₂—, —C≡CCH₂O—, —C≡CCH₂OCH₂— or —OC≡CCH₂—.

A three- to ten-membered mono- or bi-cyclic ring system Ra₁ or Ra₂, which may be interrupted once or up to three times selected from oxygen, sulfur, S(O), SO₂, N(Ra₆), carbonyl and C(═NORa₇) and which is bonded to the carbon atom of the substituent A₁ or to the group Q₁ or Q₂ either directly or by way of a C₁-C₄alkylene, C₁-C₄alkenylene or C₂-C₄alkynylene bridge which may be interrupted by oxygen, —N(C₁-C₄alkyl)-, sulfur, sulfinyl or by sulfonyl, is to be understood as being, for example, 1-methyl-1H-pyrazol-3-yl, 1-ethyl-1H-pyrazol-3-yl, 1-propyl-1H-pyrazol-3-yl, 1H-pyrazol-3-yl, 1,5-dimethyl-1H-pyrazol-3-yl, 4-chloro-1-methyl-1H-pyrazol-3-yl, 1H-pyrazol-1-yl, 3-methyl-1H-pyrazol-1-yl, 3,5-dimethyl-1H-pyrazol-1-yl, 3-isoxazolyl, 5-methyl-3-isoxazolyl, 3-methyl-5-isoxazolyl, 5-isoxazolyl, 1H-pyrrol-2-yl, 1-methyl-1H-pyrrol-2-yl, 1H-pyrrol-1-yl, 1-methyl-1H-pyrrol-3-yl, 2-furyl, 5-methyl-2-furyl, 3-furyl, 5-methyl-2-thienyl, 2-thienyl, 3-thienyl, 1-methyl-1H-imidazol-2-yl, 1H-imidazol-2-yl, 1-methyl-1H-imidazol-4-yl, 1-methyl-1H-imidazol-5-yl, 4-methyl-2-oxazolyl, 5-methyl-2-oxazolyl, 2-oxazolyl, 2-methyl-5-oxazolyl, 2-methyl-4-oxazolyl, 4-methyl-2-thiazolyl, 5-methyl-2-thiazolyl, 2-thiazolyl, 2-methyl-5-thiazolyl, 2-methyl-4-thiazolyl, 3-methyl-4-isothiazolyl, 3-methyl-5-isothiazolyl, 5-methyl-3-isothiazolyl, 1-methyl-1H-1,2,3-triazol-4-yl, 2-methyl-2H-1,2,3-triazol-4-yl, 4-methyl-2H-1,2,3-triazol-2-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 1,5-dimethyl-1H-1,2,4-triazol-3-yl, 3-methyl-1H-1,2,4-triazol-1-yl, 5-methyl-1H-1,2,4-triazol-1-yl, 4,5-dimethyl-4H-1,2,4-triazol-3-yl, 4-methyl-4H-1,2,4-triazol-3-yl, 4H-1,2,4-triazol-4-yl, 5-methyl-1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-4-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 4-methyl-3-furazanyl, 3-furazanyl, 5-methyl-1,2,4-oxadiazol-2-yl, 5-methyl-1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-4-yl, 3-methyl-1,2,4-thiadiazol-5-yl, 5-methyl-1,2,4-thiadiazol-3-yl, 4-methyl-1,2,5-thiadiazol-3-yl, 5-methyl-1,3,4-thiadiazol-2-yl, 1-methyl-1H-tetrazol-5-yl, 1H-tetrazol-5-yl, 5-methyl-1H-tetrazol-1-yl, 2-methyl-2H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 5-methyl-2H-tetrazol-2-yl, 2H-tetrazol-2-yl, 2-pyridyl, 6-methyl-2-pyridyl, 4-pyridyl, 3-pyridyl, 6-methyl-3-pyridazinyl, 5-methyl-3-pyridazinyl, 3-pyridazinyl, 4,6-dimethyl-2-pyrimidinyl, 4-methyl-2-pyrimidinyl, 2-pyrimidinyl, 2-methyl-4-pyrimidinyl, 2-chloro-4-pyrimidinyl, 2,6-dimethyl-4-pyrimidinyl, 4-pyrimidinyl, 2-methyl-5-pyrimidinyl, 6-methyl-2-pyrazinyl, 2-pyrazinyl, 4,6-dimethyl-1,3,5-triazin-2-yl, 4,6-dichloro-1,3,5-triazin-2-yl, 1,3,5-triazin-2-yl, 4-methyl-1,3,5-triazin-2-yl, 3-methyl-1,2,4-triazin-5-yl, 3-methyl-1,2,4-triazin-6-yl,

wherein each R₂₆ is methyl, each R₂₇ independently is hydrogen, C₁-C₃alkyl, C₁-C₃alkoxy, C₁-C₃alkylthio or trifluoromethyl, and X₉ is oxygen or sulfur.

A further annellated (fused-on), monocyclic or bicyclic ring system which is formed, for example, by two adjacent substituents Ra₁ and Ra₂ or Ra₁ and Ra₅ and which is interrupted once or up to three times selected from oxygen, sulfur, S(O), SO₂, —N(Ra₆)—, carbonyl and C(═NORa₇) and which may be additionally substituted by one or more substituents is to be understood as being, for example, an annellated, bidentate ring system of formula

wherein especially R₄₆ is hydrogen, halogen, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy or C₁-C₄alkylthio; R₄₇ is hydrogen, halogen, C₁-C₄alkyl or C₁-C₄alkoxy, R₅₀, R₅₁, R₅₂, R₅₃, R₅₄, R₅₅, R₅₆, R₅₇, R₅₈ and R₅₉ are each independently of the others hydrogen or C₁-C₄alkyl; and X₁₀ is oxygen or NOR₅₉.

A heteroaryl group Y substituted at least in the ortho position is to be understood as being especially a 5- or 6-membered aromatic heteroaryl group as defined hereinbefore which is, in addition, substituted once or up to three times by substituents selected from the meanings of Ra₁, Ra₂, Ra₃ and Ra₄ and Ra₅ at the nitrogen and/or at the carbon atoms.

Using the process according to the invention it is possible, especially advantageously, to prepare the cyclohexanedione herbicides described in WO 00/1 5615, WO 00/37437, WO 01/66522 and WO 01/94339.

Compounds of formula I that are highly suitable for preparation using the process according to the invention are those wherein

R₁ and R₂ are hydrogen;

Q is Q₁, wherein A₄ is CRa₁ or N—(O)_(p);

p is 0;

Ra₁ is hydrogen, C₁-C₆alkyl, hydroxy, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃-C₆alkenyloxy, C₃-C₆haloalkenyloxy, C₃-C₆alkynyloxy, C₁-C₄alkoxy-C₁-C₂alkoxy, C₁-C₄alkoxy-C₁-C₂alkoxy-C₁-C₂alkoxy, (C₃-C₆cycloalkyl)-C₁-C₂alkoxy, (1,3-dioxolan-2-yl)-C₁-C₂alkoxy, (tetrahydrofuran-2-yl)-C₁-C₂alkoxy, (tetrahydro-furan-3-yl)oxy, (oxetan-3-yl)oxy, (C₃-C₆cycloalkyl)oxy, C₁-C₄alkylsulfonyloxy, C₁-C₄alkylthio, C1-C₄alkylsulfonyl, C₁-C₄alkylamino, di(C₁-C₄alkyl)amino, C₁-C₂alkoxyethylamino, C₁-C₂alkoxyethyl-(N-methyl)amino, morpholino, C₁-C₄alkylcarbonylaminoethoxy, C₁-C₄alkoxycarbonyl, hydroxymethyl, C₁-C₆alkoxymethyl, C₁-C₆haloalkoxymethyl, C₃-C₆alkenyloxymethyl, C₃-C₆haloalkenyloxymethyl, C₃-C₆alkynyloxymethyl, C₁-C₄alkoxy-C₁-C₂alkoxymethyl, (C₃-C₆cycloalkyl)methoxymethyl, (1,3-dioxolan-2-yl)methoxymethyl, (tetrahydro-furan-2-yl)methoxymethyl, (tetrahydro-furan-3-yl)oxymethyl, (oxetan-3-yl)oxymethyl, (C₃-C₆cycloalkyl)oxymethyl, C₁-C₄alkylcarbonylamino-C₁-C₂alkoxy, C₁-C₄haloalkyl, cyano, halogen, phenyl or benzyloxy, it being possible for a phenyl-containing group in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro;

Ra₂ is C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆alkenyl, C₂-C₆haloalkenyl, C₂-C₆alkynyl, C₃-C₆-cycloalkyl, halo- or C₁-C₂alkoxymethyl-substituted C₃-C₆cycloalkyl, C₁-C₆alkoxy, C₃-C₆-alkenyloxy, C₃-C₆alkynyloxy, C₁-C₆haloalkoxy, C₃-C₆haloalkenyloxy, C₁-C₄alkoxy-C₁-C₄-alkoxy, C₁-C₄alkylthio-C₁-C₄alkoxy, C₁-C₄alkylsulfinyl-C₁-C₄alkoxy, C₁-C₄alkylsulfonyl-C₁-C₄-alkoxy, C₁-C₄alkoxycarbonyl-C₁-C₄alkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, C₁-C₆haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl, C₁-C₆alkylaminosulfonyl, di(C₁-C₆alkyl)aminosulfonyl, C₁-C₄alkylsulfonyloxy, C₁-C₄haloalkylsulfonyloxy, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄-alkyl), cyano, halogen, hydroxy-C₁-C₄-alkyl, C₁-C₄alkoxy-C₁-C₄alkyl, C₁-C₄alkylthio-C₁-C₄alkyl, C₁-C₄alkylsulfinyl-C₁-C₄alkyl, C₁-C₄alkylsulfonyl-C₁-C₄alkyl, cyano-C₁-C₄alkyl, Cl-b₆alkylcarbonyloxy-C₁-C₄alkyl, C₁-C₄alkoxycarbonyl-C₁-C₄alkyl, C₁-C₄alkoxycarbonyloxy-C₁-C₄alkyl, phenoxy-C₁-C₄alkyl, benzyloxy-C₁-C₄alkyl, benzoyloxy-C₁-C₄alkyl, benzyloxy, benzylthio, phenoxy or phenylthio, it being possible for the phenyl-containing groups in turn to be substituted by C₁-C₃alkyl, C₁-C₃haloalkyl, C₁-C₃alkoxy, C₁-C₃haloalkoxy, halogen, cyano or by nitro; or

Ra₂ is the group -X₁-X₃ or the group -X₂-X₁-X₃, wherein X₁, X₂ and X₃ are as defined hereinbefore; or

Ra₃ is hydrogen; or

Ra₄ is hydrogen or methyl; or

Ra₅ is C₁-C₆haloalkyl, C₂-C₆haloalkenyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆alkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylthio, Cl-C6haloalkylsulfinyl, C₁-C₆haloalkylsulfonyl, C₁-C₆alkylsulfonyloxy, C₁-C₄alkylaminosulfonyl, di(C₁-C₄alkyl)aminosulfonyl, C₁-C₄alkylsulfonylamino, C₁-C₄alkylsulfonyl-N(C₁-C₄alkyl)-, cyano, halogen, C₁-C₄alkoxymethyl, C₁-C₄alkylthiomethyl, C₁-C₄alkylsulfinylmethyl, C₁-C₄alkylsulfonylmethyl or 1H-1,2,4-triazol-1-yl.

Compounds of formula I that are especially highly suitable for preparation using the process according to the invention are those wherein

R₂ and R₅ together are ethylene;

R₁ and R₆ are hydrogen;

A₂ is C(R₃R₄)n, wherein R₃ and R₄ are hydrogen and n is 1.

The process according to the invention is explained in greater detail by the following Examples.

Reaction Step A

A preferred bromination agent is oxalyl bromide. A suitable chlorination agent is thionyl chloride, oxalyl chloride or phosgene. The reaction may be carried out in the presence of a base such as, for example, a tertiary amine or heterocyclic amine, or an inorganic carbonate or hydrogen carbonate. The reaction may furthermore be carried out without the addition of base in the presence of a catalytic amount of a tertiary amide such as, for example, dimethylformamide. The reaction of the compound of formula II with the compound of formula III is carried out in the presence of a base such as, for example, a tertiary amine or heterocyclic amine, or an inorganic carbonate and a catalytic amount of a tertiary amide such as, for example, dimethylformamide, R₉ preferably being methyl. Reaction Step a) may be carried out at temperatures from 0° C. to 100° C.

Suitable solvents are ethers, hydrocarbons or chlorinated hydrocarbons.

Compounds of formula 11 are known; they are commercially available in some cases or can be prepared by known methods.

The intermediates of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z₁ is chlorine, bromine or OSO₂R₉, R₉ being as defined for formula III, are novel and were developed specifically for the present process, and the present invention accordingly also relates thereto.

Especially preferred intermediates are the compounds of formulae IVa and IVb

wherein Z₂ is chlorine, bromine or OSO₂R₉, R₉ being as defined for formula III but preferably being methyl.

Reaction Step B

Reaction Step b) is carried out in the absence of water and in the presence of a base, for example a tertiary amine, preferably triethylamine or diisopropylethylamine. The reaction is preferably carried out in the presence of a solvent such as a hydrocarbon, acetonitrile, ether or dipolar aprotic solvent. When Z₁ is OSO₂R₉, the reaction is preferably carried out in chlorobenzene, toluene, acetonitrile or tetrahydrofuran. For activation of the leaving group Z₁, the presence of a catalyst such as, for example, a Lewis acid such as ZnCl₂ or AgClO₄ is advantageous. When Z₁ is chlorine or bromine, the reaction is preferably carried out in the presence of acetonitrile, toluene, xylene or chlorobenzene as solvent. When Z₁ is OSO₂R₉, the reaction temperatures are from 0° C. to 150° C., preferably from 0° C. to 100° C. When Z₁ is chlorine or bromine, the reaction is preferably carried out at temperatures of from 80° C. to 130° C.

Reaction Step C

In an especially preferred embodiment of the process according to the invention, the reaction according to Reaction Step c) is carried out without isolation of intermediates, that is to say the compound of formula VI obtained according to Reaction Step b) is treated in situ with cyanide ions in the presence of a base.

The cyanide ions are preferably used in amounts of from 0.01% to 15%. The reaction is preferably carried out at a temperature of from 50° C. to 150° C., especially at from 50° C. to 100° C., in the absence of water and in the presence of a base, for example from 0.1 to 2.5 equivalents of triethylamine, or Hünig's base.

A suitable cyanide ion source is, for example, sodium cyanide, potassium cyanide, copper(I) cyanide, acetone cyanohydrin or trimethylsilyl cyanide, preferably potassium cyanide. Suitable solvents for Reaction Step c) are, for example, hydrocarbons, acetonitriles, ethers, chlorinated hydrocarbons and dipolar aprotic solvents. Such enol ester rearrangements are described, for example, in EP-A-0 186 117.

In a very especially preferred embodiment of the process according to the invention, Reaction Steps a), b) and c) are carried out without isolation of intermediates, in the form of a one-pot reaction. The possibility of carrying out the process according to the invention in a one-pot reaction constitutes a considerable advantage especially for large-scale application.

The process according to the invention will be explained in greater detail in the following Preparation Examples:

EXAMPLE P1 Preparation of 3-bromobicyclo[3.2.1]oct-2-en-1-one

To a solution of 5 g (34.4 mmol) of bicyclo[3.2.1]octane-2,4-dione (preparation in accordance with JP 10265441 A2) in 50 ml of dichloromethane there are added, in succession, with stirring, 0.05 ml of dimethylformamide and then, over the course of 15 minutes, 8.9 g (41.3 mmol) of oxalyl bromide in portions, during which gas is evolved. The exothermic reaction is controlled using a water bath. The resulting light-brown solution is stirred for one hour at ambient temperature. The reaction mixture is then washed with 50 ml of 1M sodium hydrogen carbonate solution, a high degree of foaming being observed, and is then dried using magnesium sulfate. After removal of the solvent in vacuo, 4.8 g (56% of theory) of 3-bromobicyclo[3.2.1]oct-2-en-1-one are obtained in the form of a dark-brown oil.

MS: 202 (M⁺ ⁸¹Br isotope), 200 (M⁺ ⁷⁹Br isotope), 161, 159, 133, 131, 121, 91, 77, 65, 51, 39

¹H NMR (CDCl₃): 1.60-1.70 (m, 2H), 1.85-1.95 (m, 1H), 1.95-2.05 (m, 1H), 2.10-2.20 (m, 2H), 2.95 (m,1H), 3.20 (m,1H), 6.20 (s,1H).

EXAMPLE P2 3-Chlorobicyclo[3.2.1]oct-2-en-1-one

To a solution of 4.8 g (32.8 mmol) of bicyclo[3.2.1]octane-2,4-dione in 50 ml of dichloromethane there are added, in succession, with stirring, 0.05 ml of dimethylformamide and then, over the course of 30 minutes, 5 g (39.4 mmol) of oxalyl chloride in portions, during which gas is evolved. The exothermic reaction is controlled using a water bath. The resulting red-brown solution is stirred for 30 minutes at ambient temperature. The reaction mixture is divided into two equal portions. One portion of the reaction mixture is then washed with 50 ml of 1M sodium hydrogen carbonate solution, a high degree of foaming being observed. After removal of the solvent in vacuo, 1.9 g (70% of theory) of 3-chlorobicyclo[3.2.1]oct-2-en-1-one are obtained in the form of a brown oil.

MS: 158 (M⁺ ³⁷Cl isotope), 156 (M⁺ ³⁵Cl isotope), 117, 115, 91, 87, 77, 65, 51, 39

¹H NMR (CDCl₃): 1.60-1.70 (m, 2H), 1.80-1.95 (m, 1H), 2.00-2.10 (m, 1H), 2.15-2.25 (m, 2H), 2.95 (m, 1H), 3.05 (m, 1H), 6.00 (s, 1H)

EXAMPLE P3 Preparation of 4-oxo-bicyclo[3.2.1]oct-2-en-2-yl-methanesulfonic acid ester

13.82 g (100 mmol) of bicyclo[3.2.1]octane-2,4-dione, 11.46 g (100 mmol) of methanesulfonyl chloride and 15.18 g (150 mmol) of triethylamine are heated in 100 ml of chloroform at a temperature of from 60 to 65° C. with stirring for 24 hours. 15.3 g of 4-oxo-bicyclo-[3.2.1]oct-2-en-2-yl-methanesulfonic acid ester in the form of a brown, gum-like product are obtained, which can be used for the next Reaction Step without further purification.

¹H NMR (CDCl₃): 1.6-1.75 (m, 2H), 1.9-2.2 (m, 4H), 2.9-3.0 (m, 2H, bridgehead), 3.25 (s, 3H, CH₃SO₃—), 5.8 (s, 1H, vinyl).

EXAMPLE P4 Preparation of 2-phenylcarbonyloxy-4-oxo-bicyclo[3.2.1]oct-2-ene

2.165 g (10 mmol) of 4-oxo-bicyclo[3.2.1]oct-2-en-2-yl-methanesulfonic acid ester (Preparation Example P3), 1.34 g (11 mmol) of benzoic acid and 1.52 g (15 mmol) of triethylamine in 20 ml of chlorobenzene are heated with stirring for 8 hours. The cooled reaction mixture is then washed with 5% aqueous sulfuric acid and 5% aqueous sodium hydroxide. The organic phase is dried over sodium sulfate and concentrated to dryness by evaporation in vacuo. 2.99 g of 2-phenylcarbonyloxy-4-oxo-bicyclo[3.2.1]oct-2-ene are obtained in the form of a brown oil.

¹H NMR (CDCl₃): 1.65-1.8 (m, 2H), 2.0-2.4 (m, 4H), 2.95-3.1 (m, 2H, bridgehead), 5.85 (s, 1H, vinyl), 6.95-7.05 (m, 2H, aryl), 7.1-7.2 (m, 1H, aryl), 8.05-8.15 (m, 2H, aryl).

EXAMPLE P5 Preparation of 3-(2-nitro-4-methylsulfonyl-phenylcarbonyloxy)-cyclohex-2-en-1-one

To a mixture of 157 mg (1.15 mmol) of 3-chlorocyclohex-2-en-1-one (prepared as described in Synthesis (1974), (1), 47-8), 16 mg (0.12 mmol) of ZnCl₂, 297 mg (1.15 mmol) of 2-nitro-4-methylsulfonylbenzoic acid and 3 ml of anhydrous acetonitrile there are added dropwise, under a nitrogen atmosphere, over the course of 15 minutes, 166 mg (1.27 mmol) of diisopropylethylamine. A further 2 ml of acetonitrile are then added and, with stirring, the reaction mixture is maintained at a temperature of 45° C. for 18 hours in an oil bath. The reaction mixture is then heated up again and maintained at reflux temperature for 40 hours.

The reaction mixture is then brought to ambient temperature and the solvent is removed in vacuo. 25 ml of dichloromethane and 0.35 g of 36% hydrochloric acid in 5 ml of water are then added and the phases are separated. The organic phase is washed twice with 10 ml of water, dried using magnesium sulfate and concentrated in vacuo. 197 mg of 3-(2-nitro-4-methylsulfonyl-phenylcarbonyloxy)-cyclohex-2-en-1-one are obtained in the form of a brown oil.

¹H NMR (CDCl₃): 2.10-2.20 (m, 2H), 2.45-2.50 (m, 2H), 2.70-2.75 (m, 2H), 3.20 (s, 3H, CH₃SO₂), 6.10 (s, 1 H, C═CH), 8.00 (d, 1 H, ar. H), 8.35 (d, 1H, ar. H), 8.65 (s, 1H, ar. H).

EXAMPLE P6 Preparation of 3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-cyclohex-2-en-1-one

To a mixture of 157 mg (1.15 mmol) of 3-chlorocyclohex-2-en-1-one, 16 mg (0.12 mmol) of ZnCl₂, 324 mg (1.15 mmol) of 2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid (preparation described in WO 2001094339) and 2 ml of toluene there are added dropwise, under a nitrogen atmosphere, over the course of 15 minutes, 166 mg (1.27 mmol) of diisopropylethylamine. A further 2 ml of toluene are then added and, with stirring, the reaction mixture is maintained under moderate reflux for 18 hours in an oil bath. The reaction mixture is then brought to ambient temperature and 30 ml of dichloromethane and 20 ml of water are added. The organic phase is separated off and washed twice with 0.1M hydrochloric acid (20 ml) and twice with water (10 ml). After drying using magnesium sulfate and concentration in vacuo, 226 mg of 3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-cyclohex-2-en-1-one are obtained in the form of an orange-brown oil.

MS: 373 (M⁺), 354, 328, 262, 230, 202, 187, 159, 139, 109, 95, 59, 45.

¹H NMR (CDCl₃): 2.10-2.20 (m, 2H), 2.45-2.50 (m, 2H), 2.70-2.75 (m, 2H), 3.35 (s, 3H, CH₃O), 3.50 (CH₂CH₂O), 3.70 (OCH₂CH₂), 5.00 (s, 2H, ar. CH₂), 6.10 (s, 1H, C═CH), 7.75 (d, 1 H, ar. H), 8.30 (d, 1H, ar. H).

EXAMPLE P7 Preparation of 4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-yl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 200 mg (1.15 mmol) of 4-chlorobicyclo[3.2.1]oct-3-en-2-one, (Preparation Example P2) 16 mg (0.12 mmol) of ZnCl₂, 324 mg (1.15 mmol) of 2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid, 166 mg (1.27 mmol) of diisopropylethylamine and 5 ml of toluene is stirred under a nitrogen atmosphere at room temperature until a clear brown solution having a white sediment is formed. The reaction mixture is then maintained under moderate reflux for 26 hours in an oil bath, with stirring. The reaction mixture is then cooled to ambient temperature and 30 ml of dichloromethane are added. The solution is then washed twice with water (20 ml each time) and then twice with 0.1M hydrochloric acid (20 ml each time) and again twice with water (15 ml each time). After drying the organic solution using magnesium sulfate and concentrating in vacuo, 284 mg of 4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one are obtained in the form of a brown oil.

MS: 399(M⁺), 380, 354, 262, 230, 204, 187, 159, 139, 121, 91.

¹H NMR (CDCl₃): 1.65-1.75 (m,2H), 2.05-2.30 (m, 4H), 3.00 (br t, 1H), 3.10 (br s, 1H), 3.35 (s, 3H, OCH₃), 3.50 (m, 2H, CH₂CH₂O), 3.70 (m, 2H, OCH2CH₂), 5.00 (s, 2H, ar. CH2), 5.90 (s,1H. C═CH), 7.75 (d,1H. ar. H), 8.30 (d,1H. ar. H).

EXAMPLE P8 Preparation of 4-(4-chlorophenyl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 500 mg of 4-chlorobicyclo[3.2.1]oct-3-en-2-one (Preparation Example P2), 440 mg of ZnCl₂, 400 mg of 4-chlorobenzoic acid, 1.05 g of diisopropylethylamine and 5 ml of toluene is stirred at room temperature under a nitrogen atmosphere at reflux temperature for 6 hours. After cooling, the reaction mixture is then diluted with dichloromethane and washed with 5% aqueous sulfuric acid and 5% aqueous sodium hydroxide. After concentration of the organic phase to dryness by evaporation, 0.6 g of 4-(4-chlorophenyl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one is obtained.

¹H NMR (CDCl₃): 1.65-1.8 (m, 2H), 2.0-2.4 (m, 4H), 2.95-3.1 (m, 2H, bridgehead), 5.85 (s, 1H, vinyl), 6.95-7.05 (m, 2H, aryl), 8.0-8.1 (m, 2H, aryl).

EXAMPLE P9 Preparation of 4-phenyl-carbonyloxy-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 500 mg of 4-chlorobicyclo[3.2.1]oct-3-en-2-one (Preparation Example P2), 440 mg of ZnCl₂, 400 mg of 4-benzoic acid, 1.05 g of diisopropylethylamine and 5 ml of toluene is stirred at room temperature under a nitrogen atmosphere at reflux temperature for 8 hours. After cooling, the reaction mixture is then diluted with dichloromethane and washed with 10% aqueous sulfuric acid. After concentration of the organic phase to dryness by evaporation, 0.4 g of 4-phenyl-carbonyloxy-bicyclo[3.2.1]oct-3-en-2-one is obtained.

¹H NMR (CDCl₃): 1.65-1.8 (m, 2H), 2.0-2.4 (m, 4H), 2.95-3.1 (m, 2H, bridgehead), 5.85 (s, 1H, vinyl), 6.95-7.05 (m, 2H, aryl), 7.1-7.2 (m, 1H, aryl), 8.05-8.15 (m, 2H, aryl).

EXAMPLE P10 Preparation of 4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-yl-carbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one

A mixture of 27 g of a 6.2% solution of 4-bromobicyclo[3.2.1]oct-3-en-2-one (Preparation Example P1) in chlorobenzene, 110 mg of ZnCl₂, 2.34 g of 2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid and 1.2 g of Hünig's base is stirred at room temperature under a nitrogen atmosphere until a dark-brown solution is formed. The reaction mixture is then maintained under moderate reflux for 19 hours in an oil bath, with stirring. The mixture is then divided into 2 portions. To one portion there are added a further 1.12 g of 2-methoxyethoxymethyl-6-trifluoromethylnicotinic acid, 0.06 g of ZnCl₂ and 0.6 g of Hünig's base. The reaction mixture is then maintained under moderate reflux for 12 hours in an oil bath, with stirring. The solution is then washed twice with 0.1M hydrochloric acid (20 ml each time) and twice with water (20 ml each time). After drying the organic solution using magnesium sulfate and concentrating in vacuo, 3.9 g of 4-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyloxy)-bicyclo[3.2.1]oct-3-en-2-one are obtained in the form of a brown oil.

MS: 399 (M⁺), 380, 354, 262, 230, 202, 187, 159, 139, 121, 91.

¹H NMR (CDCl₃: 1.65-1.75 (m, 2H), 2.05-2.30 (m, 4H), 3.00 (br t, 1H), 3.10 (br s, 1H), 3.35 (s, 3H, OCH₃), 3.50 (m, 2H, CH₂CH2O), 3.70 (m, 2H, OCH₂CH₂), 5.00 (s, 2H, ar. CH₂), 5.90 (s, 1H, C═CH), 7.75 (d, 1H. ar. H), 8.30 (d, 1H. ar. H).

EXAMPLE P11 Preparation of 4-hydroxy-3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyl)-bicyclo[3.2.1]oct-3-en-2-one

To a mixture of 200 mg (1.15 mmol) of 4-chlorobicyclo[3.2.1]oct-3-en-2-one (Preparation Example P2), 16 mg (0.12 mmol) of ZnCl₂, 324 mg (1.15 mmol) of 2-methoxyethoxymethyl-6-trifluoromethyinicotinic acid and 2 ml of toluene there are added dropwise, under a nitrogen atmosphere, over the course of 15 minutes, 166 mg (1.27 mmol) of diisopropylethylamine. A further 2 ml of toluene are then added and, with stirring, the reaction mixture is maintained under moderate reflux for 23 hours in an oil bath. The reaction mixture is then cooled to ambient temperature, and 4 ml of acetonitrile, 2 drops of cyanohydrin, 465 mg of triethylamine and a further 1 ml of acetonitrile are added. After drying the organic phase using magnesium sulfate and concentrating in vacuo, 452 mg of 4-hydroxy-3-(2-methoxyethoxymethyl-6-trifluoromethyl-pyridin-3-ylcarbonyl)-bicyclo[3.2.1]oct-3-en-2-one are obtained in the form of a viscous oil.

MS: 399 (M⁺), 380, 356, 340, 310, 282, 256, 228, 202, 174, 152, 128, 67, 45.

¹H NMR (CDCl₃): 1.70-1.80 (m, 2H), 2.05-2.30 (m, 4H), 2.90 (br s,1H), 3.15 (br s, 1H), 3.30 (s, 3H, OCH₃), 3.40 (m, 2H, CH₂CH₂O), 3.50 (m, 2H, OCH₂CH₂), 4.75 (s, 2H, ar. CH₂), 7.60 (s, 2H, ar. H). 

1. A process for the preparation of a compound of formula I

wherein Y is an organic substituent which is so selected that the compound of formula I has a pK value of from 1 to 5; A₁ is CR₁R₂; A₂ is oxygen, C(O), SO₂ or (CR₃R₄)_(n); n is 1 or 2; A₃ is CR₅R₆; R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others C₁-C₄alkyl which may be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, phenyl or by heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R₁, R₂, R₃, R₄, R₅ and R₆ are each independently of the others hydrogen, C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfinyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl, phenyl or heteroaryl, it being possible for the phenyl and heteroaryl groups in turn to be mono-, di- or tri-substituted by C₁-C₄alkoxy, halogen, hydroxy, cyano, hydroxycarbonyl, C₁-C₄alkoxycarbonyl, C₁-C₄alkylsulfonyl or by C₁-C₄haloalkyl, the substituents on the nitrogen in the heterocyclic ring being other than halogen; and/or R₁ and R₂ together form a 3- to 5-membered carbocyclic ring which may be substituted by C₁-C₄alkyl and/or interrupted by oxygen, sulfur, S(O), SO₂, OC(O), NR₇ or by C(O); and/or R₂ and R₄ together or R₂ and R₅ together form a C₁-C₃alkylene chain which may be interrupted by oxygen, sulfur, SO, SO₂, OC(O), NR₈ or by C(O); it being possible for that C₁-C₃alkylene chain in turn to be substituted by C₁-C₄alkyl; and R₇ and R₈ are each independently of the other C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkylsulfonyl, C₁-C₄alkylcarbonyl or C₁-C₄alkoxycarbonyl; in which process a) a compound of formula II

wherein A₁, A₂ and A₃ are as defined for formula I, is reacted, in the presence of a water-immiscible solvent, in the presence of a base or a catalytic amount of a tertiary amide, either with a chlorination or bromination agent or with a compound of formula III Cl—SO₂R₉   (III), wherein R₉ is C₁-C₄alkyl, C₁-C₄haloalkyl, phenyl or C₁-C₄alkyl-substituted phenyl, to form the compound of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z₁ is chlorine, bromine or OSO₂R₉, R₉ being as defined hereinbefore; b) the compound of formula IV is converted, using a compound of formula V M⁺—O⁻—C(O)—Y   (V), wherein Y is as defined hereinbefore and M⁺ is the hydrogen cation or an alkali metal ion, alkaline earth metal ion or ammonium ion, into the compound of formula VI

and c) then the compound of formula VI is treated with a cyanide source in the presence of a base.
 2. A compound of formula IV

wherein A₁, A₂ and A₃ are as defined for formula I and Z₁ is chlorine, bromine or OSO₂R₉, R₉ being as defined for formula III in claim
 1. 3. Compounds of formulae IVa and IVb

wherein Z₂ is chlorine, bromine or OSO₂R₉, R₉ being as defined for formula III in claim
 1. 